Patent GB-1466386-A (GB)
Title: Mercaptomethylpyridines and their derivatives
IPC: C07D213/53
Filed: 1974-06-12
Abstract: 1466386 Derivatives of mercaptomethylpyridine MERCK & CO Inc 12 June 1974 [15 June 1973 16 May 1974] 26176/74 Heading C2C The invention comprises compounds of formula (=Z-SR 3 ) and their pharmacutically acceptable salts wherein: R 1  is hydrogen, C 1-3  alkyl or phenyl; R 2  is hydrogen or C 1-3  alkyl; R 3  is (a) hydrogen, (b) -SO 3 H; (c) -PO 3 H 2 ; (d) N(C 1-4  alkyl)2; (e) -C(:O)-E where E is adamantyl, C 3-8  cycloalkyl, N(C 1-4  alkyl)2, phenyl, 2 - acetoxyphenyl, 2 - hydroxy - 4- (2,4 - difluorophenyl)phenyl, 3 - chloro - 4- allyloxybenzyl, α - methyl - 4 - isobutylbenzyl, α - methyl - 3 - phenoxybenzyl, α - methyl - 3- benzoylbenzyl, 1 - (6 - methoxynaphth - 2 - yl)- ethyl, α - methyl - 3 - fluoro - 4 - phenylbenzyl, α - methyl - 3 - chloro - 4 - cyclohexylbenzyl, 2- (3 - trifluoromethylanilino)phenyl, 2 - (2,3- dimethylanilino)phenyl, 2 - (2,6 - dichloro - 3- methylanilino)phenyl, 2 - (3 - trifluoromethylanilino - 3 - pyridyl, or 2 - (2 - methyl - 3- chloroanilino)-3-pyridyl; (f) -C(:O)-S-Z; (g) -C(:O)NHCH: 2 CO 2 (C 1-4  alkyl); (h) where L is -(CH 2 ) 1-5 -, -C 6 H 4 - or 1,4- piperazinylene; (i) -S-R 12  where R 12  is -CMe 2 CH(NH 2 )CO 2 H or 2-carboxyphenyl; (j) -S-Z or (k) -(S) 2-3 -Z where m is 0 or 1, x is 0, 1, 2, 3 or 4; and R is  (1) (3 or 5)-hydroxy, (2) (3, 6, or 6)-C 1-3  alkoxy, (3) 3 or 5 -O-C(:O)-E, where E is as defined above, (4) 5-carboxy, (5) 5-carbamyl, (6) 4-hydroximinomethyl, (7) 4-formyl, (8) (2, 3, 4, 5, or 6)-C 1-5  alkyl, (9) 5-carboxy-(C 1-3  alkyl), (10) (4 or 5)-C 1-3  alkyl -OC(:O)NH 2 , (11) (3 or 5) -OP(:O)(NMe 2 ) 2 , (12) (4 or 5)-C 1-3  alkyl -OP(:O)(NMe 2 ) 2 , (13) (2, 3, 4, 5, or 6)-mercapto-C 1-3  alkyl, (14) 5-(C 1-3  alkylthio)-(C 1-3  alkyl), (15) (4 or 5)-hydroxy-(C 1-3  alkyl), (16) (4 or 5)-(C 1-3  alkoxy)-(C 1-3  alkyl), (17) (4 or 5)-amino-(C 1-3  alkyl), (18) (4 or 5)-di(C 1-3  alkyl)amino-(C 1-3  alkyl), (19) (4 or 5)-C 1-3  alkyl) -O-C(:O)-E, where E is as defined above, (20) when one R is hydroxy and another R is hydroxymethyl or mercaptomethyl on an adjacent carbon, the oxygens or oxygen and sulphur thereof may be joined together through a group of formula R 4 R 5 C< where R 4  and R 5  are the same or different and each is hydrogen, C 1-6  alkyl, or phenyl, with the proviso that if R 1  and R 2  are both hydrogen, and R 3  is hydrogen, -SO 3 H, or -S-Z, (a) x is not zero; (b) R is not -CH 2 OH or -CH 2 SH if x is 1; (c) if x is 1-4, then at least one R group is other than C 1-5  alkyl or hydroxy; (d) if x is 3, one R group is -CH 3 , and another R group is -OH, or C 2-6  alkanoyl, then the third R group is other than -CH 2 OH, -CH 2 O- (C 2-6  alkanoyl), CH=NOH, -CHO, -CH 2 NH 2 , -CH 2 N(C 1-3  alkyl) 2  and the 3 and 4 R groups together are not and the proviso that if R 3  is -C(:O)-S-Z then R is not 3-hydroxy and the 3 and 4 R groups together are not -O-CR 4 R 5 -OCH 2 -. In examples, these compounds are prepared by substantially standard procedures for the interconversion or introduction of functional groups, the formation and hydrolysis of cyclic ketals (including cyclic monothioketals), the formation and ring opening of thiolactones. Details are also given for the preparation of a number of (a) non- sulphur-containing precursors of the foregoing compounds, and (b) xanthates Therapeutic compositions having anti-rheumatoid arthritis activity comprise compounds of the above formula, and may be administered orally, parenterally, rectally, topically and by inhalation spray.